FDA ex­perts of­fer a unan­i­mous en­dorse­ment for Spark’s pi­o­neer­ing AAV gene ther­a­py for blind­ness

Kather­ine High, head of R&D, Spark Ther­a­peu­tics

A pi­o­neer­ing AAV gene ther­a­py from Spark Ther­a­peu­tics $ONCE took a gi­ant stride to­ward an FDA ap­proval to­day as an out­side pan­el of ex­perts of­fered their sup­port for get­ting this game-chang­ing treat­ment in­to the mar­ket af­ter look­ing over the da­ta and hear­ing from some of the se­vere­ly sight-im­paired pa­tients whose lives had been trans­formed by this ther­a­py.

The vote was 16 to o fa­vor­ing the ben­e­fit-risk pro­file of the drug, back­ing an OK for voreti­gene nepar­vovec by the agency’s Cel­lu­lar, Tis­sue and Gene Ther­a­pies Ad­vi­so­ry Com­mit­tee and pro­vid­ing a com­pelling rea­son for the FDA to fol­low through with an his­toric first US ap­proval of a vec­tor-de­liv­ered gene ther­a­py.

“Gene ther­a­py has made my world so much more brighter,” said one young pa­tient, who went on to de­scribe how he could see the moon for the first time, go out at night, watch fa­cial ex­pres­sions, and ba­si­cal­ly live his life more nor­mal­ly in­stead of wait­ing for blind­ness to take over. And Chris­t­ian Guardi­no talked about how the treat­ment four years ago saved his sight, a span of time when the dark­ness might well have closed in.

This was no panacea. As the agency’s in­ter­nal re­view made clear, voreti­gene nepar­vovec (or Lux­tur­na) — which us­es an ade­no-as­so­ci­at­ed vi­ral vec­tor — im­proved sight us­ing the light lev­els mea­sured for the pri­ma­ry end­point, but fell far short of cur­ing reti­nal dy­s­tro­phy trig­gered by ge­net­ic RPE65 mu­ta­tions. Im­prove­ment in vi­sion is al­so lim­it­ed by the num­ber of vi­able reti­nal cells they have left at the time they’re treat­ed, ac­cord­ing to in­ves­ti­ga­tors.

Jeff Mar­raz­zo, Spark CEO

The pan­el ex­perts faced ques­tions about the dura­bil­i­ty of this eye ther­a­py, the pos­si­bil­i­ty that pa­tients will need mul­ti­ple treat­ments in or­der to pre­serve vi­sion gains, the right age to use it and the use of a com­plete­ly nov­el end­point for the pri­ma­ry goal when stan­dard vi­su­al acu­ity achieve­ments fell far short of the goal on sta­tis­ti­cal sig­nif­i­cance.

The ex­perts, though, seemed gen­er­al­ly im­pressed by the re­sults — with some reser­va­tions about the end­point — and sev­er­al were open to treat­ing very young pa­tients. Spark is sug­gest­ing three and old­er, and CEO Jeff Mar­raz­zo told me he was in­ter­est­ed in the en­cour­age­ment he heard to go even younger in some cas­es.

While a for­mal ap­proval is not guar­an­teed, it would be con­found­ing for the agency to ig­nore the pan­el and the ros­ter of pa­tients who came for­ward to talk about be­ing able to play, study and par­tic­i­pate in the kind of day-to-day ac­tiv­i­ties that had been de­nied them all their lives. An ap­proval here could well be the first of many to come, as a group of play­ers ad­vance treat­ments that use a be­nign virus to in­tro­duce a cor­rect­ed gene to fix a wide range of con­di­tions.

“It re­al­ly came to­geth­er in tri­an­gu­lat­ing a bunch of points,” Mar­raz­zo told me af­ter the land­mark vote came through, cit­ing not just the pa­tient tes­ti­mo­ny but al­so the physi­cians who were there to back up the ap­pli­ca­tion.

Mar­raz­zo isn’t of­fer­ing any price yet, and won’t un­til the ap­proval comes through. But it won’t be cheap. Es­ti­mates for one-time costs of­ten hov­er around the $1 mil­lion mark in gene ther­a­py. The CEO, who’s ob­vi­ous­ly thought quite a lot about it, says the clear path to en­sur­ing ac­cess un­der the cur­rent rules that gov­erns in­sur­ance points to a one-time charge per eye. It’s hard to of­fer an al­ter­na­tive mod­el, he adds, giv­en the kind of porta­bil­i­ty is­sues and pay­ment mod­els peo­ple have with their in­sur­ance cov­er­age to­day — but he’s in­ter­est­ed in ex­plor­ing it and see­ing what has to change to make that hap­pen.

Eigh­teen years ago, the gene ther­a­py field was near­ly shoved in­to obliv­ion af­ter the death of a pa­tient in a tri­al be­ing con­duct­ed by Penn’s James Wil­son. But over the past 10 years in­ves­ti­ga­tors, us­ing some of the same tech­nol­o­gy that Wil­son helped cre­ate, have mount­ed a mas­sive come­back ef­fort. In Spark’s case, the Chil­dren’s Hos­pi­tal of Philadel­phia played a key role in push­ing the ear­ly R&D work, giv­ing the biotech a big leg up in the race to get the first such gene ther­a­py in­to the US mar­ket.

There have been two oth­er gene ther­a­pies in Eu­rope, in­clud­ing Glax­o­SmithK­line’s Strimvelis. But they’ve been rarely used. The ques­tion now is how these treat­ments can get root­ed in the US mar­ket and then start to spread around the world.

That day looks much clos­er than it has ever been.

Kather­ine High, pres­i­dent and head of R&D at Spark Ther­a­peu­tics said:

The clin­i­cal pro­gram for Lux­tur­na in­cludes pa­tient da­ta that show ef­fi­ca­cy for up to four years on end­points in­clud­ing bi­lat­er­al mul­ti-lu­mi­nance mo­bil­i­ty test (MLMT) score change and full-field light sen­si­tiv­i­ty thresh­old (FST) test­ing, with ob­ser­va­tion on­go­ing. We look for­ward to con­tin­u­ing to work with FDA as it com­pletes its re­view of Lux­tur­na.

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Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

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